| General information |
| Database: | DB01077 |
| Objective: | Everolimus in Postmenopausal HormoneReceptor-Positive Advanced Breast Cancer |
| Authors: | Jos¨¦ Baselga |
| Title: | Everolimus in postmenopausal hormonereceptorpositive advanced breast cancer. |
| Journal: | NEJM |
| Year: | 2012 |
| PMID: | 22149876 |
| Trial Design |
| Clinical Trial Id: | NCT00863655 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | everolimus and Exemestane |
| Study Type: | international, doubleblind, phase III study |
| Key Patients Feature: | Eligible patients were postmenopausal women with ERpositive, human epidermal growth factor receptor type 2 (human epidermal growth factor receptor 2)-nonamplified advanced breast cancer whose disease was refractory to previous letrozole or anastrozole, defined as recurrence during or within 12 months after the end of adjuvant treatment or progression during or within 1 month after the end of treatment for advanced disease. Patients had to have at least one measurable lesion or mainly lytic bone lesions in the absence of measurable disease. Patients also had to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. |
| Biomarker: | hormonereceptorpositive |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | Placebo and Exemestane |
| Treatment Info: | oral everolimus or matching placebo (at a dose of 10 mg daily), in conjunction with exemestane (25 mg daily). |
| Primary End Point: | progression free survival. |
| Secondary End Point: | overall survival, overall response rate, clinical benefit rate, time to deterioration of ECOG performance status, safety, and quality of life, with the use of the European Organization for Research and Treatment of Cancer qualityoflife core questionnaire (QLQC30) and the breast cancer module (QLQBR23). |
| Patients Number: | 724 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Response rates, on the basis of local assessment, were 9.5% and 0.4% in the combinationtherapy and exemestanealone groups, respectively (P<0.001) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | At the interim analysis, median progression free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001). |
| Median OS A vs. C: | Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.034.6 months] compared with 26.6 months (95% CI 22.633.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.731.10; logrank P = 0.14). |
| Adverse Event(agent arm): | The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimusplusexemestane group vs. 1% in the placeboplusexemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). |
| Conclusions: | Everolimus combined with an aromatase inhibitor improved progression free survival in patients with hormonereceptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. |